Ivone C. Igreja Sá (Czech Republic)
Charles University - Faculty of Pharmacy Medical and Biological SciencesAuthor Of 1 Presentation
O042 - Soluble endoglin as a potential biomarker of NASH development, participating in aggravation of NASH-related changes in mouse liver (ID 107)
Abstract
Background and Aims
Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood, and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression.
Methods
Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, LC-MS analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using qRT-PCR and Western blot.
Results
The FFC diet significantly increased mouse sEng levels and hepatic expression of Eng. High levels of human sEng resulted in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirected the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by beta-oxidation combined with reduced hepatic efflux.
Conclusions
We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
Supported by Ministry of Health of the Czech Republic grant AZV 17-31754A and GAUK No.1166119.
Presenter of 1 Presentation
O042 - Soluble endoglin as a potential biomarker of NASH development, participating in aggravation of NASH-related changes in mouse liver (ID 107)
Abstract
Background and Aims
Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis with inflammation and fibrosis. Membrane endoglin (Eng) is shown to participate in fibrosis, and plasma concentrations of soluble endoglin (sEng) are increased in patients with hypercholesterolemia and type 2 diabetes mellitus. We hypothesize that NASH increases both hepatic Eng expression and sEng in blood, and that high levels of sEng modulate cholesterol and bile acid (BA) metabolism and affect NASH progression.
Methods
Three-month-old transgenic male mice overexpressing human sEng and their wild type littermates are fed for six months with either a high-saturated fat, high-fructose high-cholesterol (FFC) diet or a chow diet. Evaluation of NASH, LC-MS analysis of BA, hepatic expression of Eng, inflammation, fibrosis markers, enzymes and transporters involved in hepatic cholesterol and BA metabolism are assessed using qRT-PCR and Western blot.
Results
The FFC diet significantly increased mouse sEng levels and hepatic expression of Eng. High levels of human sEng resulted in increased hepatic deposition of cholesterol due to reduced conversion into BA, as well as redirected the metabolism of triglycerides (TAG) to its accumulation in the liver, via reduced TAG elimination by beta-oxidation combined with reduced hepatic efflux.
Conclusions
We propose that sEng might be a biomarker of NASH development, and the presence of high levels of sEng might support NASH aggravation by impairing the essential defensive mechanism protecting NASH liver against excessive TAG and cholesterol accumulation, suggesting the importance of high sEng levels in patients prone to develop NASH.
Supported by Ministry of Health of the Czech Republic grant AZV 17-31754A and GAUK No.1166119.